反应详情

Thionyl chloride (31 μl, 0.427 mmole) was added to a suspension of 6-[(2-{[(3R)-3-methoxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid 11c (40 mg, 0.085 mmole) in dichloroethane (1 ml). The reaction mixture was heated to reflux for 90 minutes, cooled to room temperature, and concentrated in vacuo. The yellow residue was dissolved in CH2Cl2 (1 ml) and cyclopropylamine (30 μl, 0.427 mmole) was added. The resulting mixture was stirred at ambient temperature for 16 hours, diluted with CH2Cl2 (10 ml), and washed with H2O (5 ml). The aqueous layer was extracted with CH2Cl2 (2×5 ml) and the combined organics were dried (Na2SO4), filtered, and concentrated in vacuo. The crude mixture was purified by silica gel chromatography (5% MeOH/EtOAc) to afford 20 mg (46%) of a pale yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ 8.58 (1H, d, J=5.3 Hz), 8.46 (1H, d, J=4.5 Hz), 8.06 (1H, s) 7.96 (1H, d, J=2.3 Hz), 7.81 (1H, J=8.7 Hz), 7.32 (1H, dd, J=2.3, 8.7 Hz), 6.75 (1H, d, J=5.3 Hz), 4.10–3.82 (4H, m), 3.61 (2H, m), 3.27, 3.24 (3H, s), 2.91 (1H, m), 2.72 (1H, m), 2.57 (3H, s), 0.76–0.70 (2H, m), 0.50–0.55 (2H, m.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 90 minutes
3. concentrationconcentrated in vacuo
4. dissolutionThe yellow residue was dissolved in CH2Cl2 (1 ml)
5. washwashed with H2O (5 ml)
6. extractionThe aqueous layer was extracted with CH2Cl2 (2×5 ml)
7. dry with materialthe combined organics were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude mixture was purified by silica gel chromatography (5% MeOH/EtOAc)